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Schematic diagram of the MEN1 disease model established by iPSCs derived from MEN1 patients and its related mechanism.
The research group of Li Yinxiong, a researcher at the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, has made progress in establishing multiple endocrine tumor disease models using patient-derived induced pluripotent stem cells (iPSCs.
This study successfully reproduced the key expression of MEN1 hyperinsulinemia by collecting urine cells from multiple endocrine tumor type I (MEN1) patients and reprogramming them into iPSCs, combining in vitro islet β-like cell differentiation and transplantation experiments in immunodeficient mic.
MEN1 is a rare genetic diseas.
In this work, we established a reprogrammed cell line by collecting urine from two mothers and sons of a MEN1 family, which reproduced the clinical manifestations of hyperinsulinemia in the islet beta-like cell stage of MEN1-iPSC differentiatio.
To explore its pathological mechanism, it was found that the secretion of glucagon-like peptide-1 (GLP-1), which is negatively regulated by MEN1, is up-regulate.
Further transplantation experiments in immunodeficient mice found that MEN1 cells at different stem cell stages could not form tumors, and only MEN1 pancreatic islet β-like cells could form tumors and express PNETs markers consistent with patients' orthotopic tumor.
Relevant research work has been supported by the National Key Research and Development Program Fund, the National Natural Science Foundation of China, and the Guangdong Provincial Basic and Applied Basic Research Fun.